+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-34044 | |||||||||
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Title | SARS-CoV-2 BA.2.75 S Trimer in complex with ACE2(state2) | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction ...positive regulation of amino acid transport / angiotensin-converting enzyme 2 / positive regulation of L-proline import across plasma membrane / Hydrolases; Acting on peptide bonds (peptidases); Metallocarboxypeptidases / angiotensin-mediated drinking behavior / regulation of systemic arterial blood pressure by renin-angiotensin / tryptophan transport / positive regulation of gap junction assembly / negative regulation of signaling receptor activity / regulation of vasoconstriction / regulation of cardiac conduction / peptidyl-dipeptidase activity / maternal process involved in female pregnancy / angiotensin maturation / Metabolism of Angiotensinogen to Angiotensins / metallocarboxypeptidase activity / carboxypeptidase activity / Attachment and Entry / positive regulation of cardiac muscle contraction / regulation of cytokine production / viral life cycle / blood vessel diameter maintenance / negative regulation of smooth muscle cell proliferation / brush border membrane / regulation of transmembrane transporter activity / cilium / negative regulation of ERK1 and ERK2 cascade / metallopeptidase activity / positive regulation of reactive oxygen species metabolic process / endocytic vesicle membrane / virus receptor activity / regulation of inflammatory response / regulation of cell population proliferation / endopeptidase activity / Potential therapeutics for SARS / Maturation of spike protein / viral translation / Translation of Structural Proteins / Virion Assembly and Release / host cell surface / host extracellular space / suppression by virus of host tetherin activity / Induction of Cell-Cell Fusion / structural constituent of virion / entry receptor-mediated virion attachment to host cell / host cell endoplasmic reticulum-Golgi intermediate compartment membrane / receptor-mediated endocytosis of virus by host cell / Attachment and Entry / membrane fusion / positive regulation of viral entry into host cell / receptor-mediated virion attachment to host cell / receptor ligand activity / symbiont-mediated suppression of host innate immune response / host cell surface receptor binding / apical plasma membrane / symbiont entry into host cell / membrane raft / endoplasmic reticulum lumen / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / SARS-CoV-2 activates/modulates innate and adaptive immune responses / host cell plasma membrane / virion membrane / cell surface / extracellular space / zinc ion binding / extracellular exosome / extracellular region / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | Severe acute respiratory syndrome coronavirus 2 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.52 Å | |||||||||
Authors | Wang L | |||||||||
Funding support | 1 items
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Citation | Journal: Cell Host Microbe / Year: 2022 Title: Characterization of the enhanced infectivity and antibody evasion of Omicron BA.2.75. Authors: Yunlong Cao / Weiliang Song / Lei Wang / Pan Liu / Can Yue / Fanchong Jian / Yuanling Yu / Ayijiang Yisimayi / Peng Wang / Yao Wang / Qianhui Zhu / Jie Deng / Wangjun Fu / Lingling Yu / Na ...Authors: Yunlong Cao / Weiliang Song / Lei Wang / Pan Liu / Can Yue / Fanchong Jian / Yuanling Yu / Ayijiang Yisimayi / Peng Wang / Yao Wang / Qianhui Zhu / Jie Deng / Wangjun Fu / Lingling Yu / Na Zhang / Jing Wang / Tianhe Xiao / Ran An / Jing Wang / Lu Liu / Sijie Yang / Xiao Niu / Qingqing Gu / Fei Shao / Xiaohua Hao / Bo Meng / Ravindra Kumar Gupta / Ronghua Jin / Youchun Wang / Xiaoliang Sunney Xie / Xiangxi Wang / Abstract: Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced ...Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a growth advantage over circulating BA.2.38, BA.2.76, and BA.5 in India. However, the underlying mechanisms for enhanced infectivity, especially compared with BA.5, remain unclear. Here, we show that BA.2.75 exhibits substantially higher affinity for host receptor angiotensin-converting enzyme 2 (ACE2) than BA.5 and other variants. Structural analyses of BA.2.75 spike shows its decreased thermostability and increased frequency of the receptor binding domain (RBD) in the "up" conformation under acidic conditions, suggesting enhanced low-pH-endosomal cell entry. Relative to BA.4/BA.5, BA.2.75 exhibits reduced evasion of humoral immunity from BA.1/BA.2 breakthrough-infection convalescent plasma but greater evasion of Delta breakthrough-infection convalescent plasma. BA.5 breakthrough-infection plasma also exhibits weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75's distinct neutralizing antibody (NAb) escape pattern. Antibody therapeutics Evusheld and Bebtelovimab remain effective against BA.2.75. These results suggest BA.2.75 may prevail after BA.4/BA.5, and its increased receptor-binding capability could support further immune-evasive mutations. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_34044.map.gz | 118.2 MB | EMDB map data format | |
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Header (meta data) | emd-34044-v30.xml emd-34044.xml | 19.5 KB 19.5 KB | Display Display | EMDB header |
Images | emd_34044.png | 26.9 KB | ||
Others | emd_34044_half_map_1.map.gz emd_34044_half_map_2.map.gz | 115.8 MB 115.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-34044 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-34044 | HTTPS FTP |
-Validation report
Summary document | emd_34044_validation.pdf.gz | 1003.1 KB | Display | EMDB validaton report |
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Full document | emd_34044_full_validation.pdf.gz | 1002.6 KB | Display | |
Data in XML | emd_34044_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | emd_34044_validation.cif.gz | 15.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34044 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-34044 | HTTPS FTP |
-Related structure data
Related structure data | 7yr3MC 7yqtC 7yquC 7yqvC 7yqwC 7yqxC 7yqyC 7yqzC 7yr0C 7yr1C 7yr2C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_34044.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.04 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_34044_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_34044_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : BA.2.75 Spike Trimer in complex with ACE2 (state2)
Entire | Name: BA.2.75 Spike Trimer in complex with ACE2 (state2) |
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Components |
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-Supramolecule #1: BA.2.75 Spike Trimer in complex with ACE2 (state2)
Supramolecule | Name: BA.2.75 Spike Trimer in complex with ACE2 (state2) / type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: #1-#2 |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 |
-Supramolecule #2: BA.2.75 Spike Trimer
Supramolecule | Name: BA.2.75 Spike Trimer / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) / Recombinant cell: HEK293 |
-Supramolecule #3: ACE2
Supramolecule | Name: ACE2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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-Macromolecule #1: Spike glycoprotein
Macromolecule | Name: Spike glycoprotein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Severe acute respiratory syndrome coronavirus 2 |
Molecular weight | Theoretical: 141.125547 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYF ASTEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLD VYYHENNKSR MESELRVYSS A NNCTFEYV ...String: MFVFLVLLPL VSSQCVNLIT RTQSYTNSFT RGVYYPDKVF RSSVLHSTQD LFLPFFSNVT WFHAIHVSGT NGTKRFDNPV LPFNDGVYF ASTEKSNIIR GWIFGTTLDS KTQSLLIVNN ATNVVIKVCE FQFCNDPFLD VYYHENNKSR MESELRVYSS A NNCTFEYV SQPFLMDLEG KQGNFKNLRE FVFKNIDGYF KIYSKHTPVN LGRDLPQGFS ALEPLVDLPI GINITRFQTL LA LHRSYLT PGDSSSSWTA GAAAYYVGYL QPRTFLLKYN ENGTITDAVD CALDPLSETK CTLKSFTVEK GIYQTSNFRV QPT ESIVRF PNITNLCPFH EVFNATRFAS VYAWNRKRIS NCVADYSVLY NFAPFFAFKC YGVSPTKLND LCFTNVYADS FVIR GNEVS QIAPGQTGNI ADYNYKLPDD FTGCVIAWNS NKLDSKVSGN YNYLYRLFRK SKLKPFERDI STEIYQAGNK PCNGV AGFN CYFPLQSYGF RPTYGVGHQP YRVVVLSFEL LHAPATVCGP KKSTNLVKNK CVNFNFNGLT GTGVLTESNK KFLPFQ QFG RDIADTTDAV RDPQTLEILD ITPCSFGGVS VITPGTNTSN QVAVLYQGVN CTEVPVAIHA DQLTPTWRVY STGSNVF QT RAGCLIGAEY VNNSYECDIP IGAGICASYQ TQTKSHRAAA SVASQSIIAY TMSLGAENSV AYSNNSIAIP TNFTISVT T EILPVSMTKT SVDCTMYICG DSTECSNLLL QYGSFCTQLK RALTGIAVEQ DKNTQEVFAQ VKQIYKTPPI KYFGGFNFS QILPDPSKPS KRSPIEDLLF NKVTLADAGF IKQYGDCLGD IAARDLICAQ KFNGLTVLPP LLTDEMIAQY TSALLAGTIT SGWTFGAGP ALQIPFPMQM AYRFNGIGVT QNVLYENQKL IANQFNSAIG KIQDSLSSTP SALGKLQDVV NHNAQALNTL V KQLSSKFG AISSVLNDIL SRLDPPEAEV QIDRLITGRL QSLQTYVTQQ LIRAAEIRAS ANLAATKMSE CVLGQSKRVD FC GKGYHLM SFPQSAPHGV VFLHVTYVPA QEKNFTTAPA ICHDGKAHFP REGVFVSNGT HWFVTQRNFY EPQIITTDNT FVS GNCDVV IGIVNNTVYD PLQPELDSFK EELDKYFKNH TSPDVDLGDI SGINASVVNI QKEIDRLNEV AKNLNESLID LQEL GKYEQ YIKWPWYIWL GFIAGLIAIV MVTIMLCCMT SCCSCLKGCC SCGSCCKFDE DDSEPVLKGV KLHYT |
-Macromolecule #2: Angiotensin-converting enzyme 2
Macromolecule | Name: Angiotensin-converting enzyme 2 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: angiotensin-converting enzyme 2 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 69.982562 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSV LSEDKSKRLN TILNTMSTIY STGKVCNPDN PQECLLLEPG LNEIMANSLD YNERLWAWES WRSEVGKQLR P LYEEYVVL ...String: STIEEQAKTF LDKFNHEAED LFYQSSLASW NYNTNITEEN VQNMNNAGDK WSAFLKEQST LAQMYPLQEI QNLTVKLQLQ ALQQNGSSV LSEDKSKRLN TILNTMSTIY STGKVCNPDN PQECLLLEPG LNEIMANSLD YNERLWAWES WRSEVGKQLR P LYEEYVVL KNEMARANHY EDYGDYWRGD YEVNGVDGYD YSRGQLIEDV EHTFEEIKPL YEHLHAYVRA KLMNAYPSYI SP IGCLPAH LLGDMWGRFW TNLYSLTVPF GQKPNIDVTD AMVDQAWDAQ RIFKEAEKFF VSVGLPNMTQ GFWENSMLTD PGN VQKAVC HPTAWDLGKG DFRILMCTKV TMDDFLTAHH EMGHIQYDMA YAAQPFLLRN GANEGFHEAV GEIMSLSAAT PKHL KSIGL LSPDFQEDNE TEINFLLKQA LTIVGTLPFT YMLEKWRWMV FKGEIPKDQW MKKWWEMKRE IVGVVEPVPH DETYC DPAS LFHVSNDYSF IRYYTRTLYQ FQFQEALCQA AKHEGPLHKC DISNSTEAGQ KLFNMLRLGK SEPWTLALEN VVGAKN MNV RPLLNYFEPL FTWLKDQNKN SFVGWSTDWS PYADHHHHHH |
-Macromolecule #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 4 / Number of copies: 53 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #6: CHLORIDE ION
Macromolecule | Name: CHLORIDE ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: CL |
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Molecular weight | Theoretical: 35.453 Da |
-Macromolecule #7: water
Macromolecule | Name: water / type: ligand / ID: 7 / Number of copies: 142 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.52 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 313740 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |